Detoxification is a mainstay of treatment for opioid dependence, but the majority of patients treated in this way relapse to opioid misuse leading to a costly and ineffectual cycle of readmission for repeated detoxification. NIDA's National Drug Abuse Treatment Clinical Trials Network (CTN) has initiated a randomized trial (CTN- 0051) that will assess the comparative effectiveness of preventing opioid dependence relapse after detoxification with extended-release injectable naltrexone (XR-NTX) and buprenorphine-naloxone (BUP-NX). These two FDA-approved medication-assisted outpatient opioid dependence treatments offer promising alternatives for opioid dependence treatment in office-based medical settings, avoiding the inconvenience and stigma associated with methadone maintenance treatment, but the medications are relatively expensive and their benefits to patients and society have not been rigorously compared to their costs. We propose to conduct an economic evaluation of XR-NTX and BUP-NX using patient-specific and site-level data collected during the CTN-0051 trial. Collecting data simultaneously on both costs and outcomes in the same trial improves the internal validity of economic analyses. We will also explore potential economic implications of findings from genetic data analyses being conducted in the CTN-0051 trial. We have assembled a uniquely qualified collaborative team of economic and health policy researchers to complete these analyses. Our specific aims are to: 1) estimate and compare costs of opioid dependence treatment with XR-NTX and BUP-NX from the perspectives of the treatment provider, the payer, and the patient; 2) estimate and compare quality-adjusted life year (QALY) outcomes for opioid dependence treatment with XR-NTX and BUP-NX; 3) from a societal perspective, evaluate the incremental cost-effectiveness and cost-benefit of opioid dependence treatment with XR-NTX compared to BUP-NX (as well as the incremental cost-effectiveness of a personalized treatment selection strategy); and 4) conduct an exploratory evaluation of the potential cost-effectiveness of pre- treatment testing for genetic variants (e.g. OPRM1, OPRK1, PDYN) associated with responses to opioid dependence treatment with XR-NTX or BUP-NX. This economic evaluation study will efficiently leverage the investment currently being made in the CTN-0051 clinical trial, and will provide rigorous and policy-relevant findings to a variety of stakeholders about the cost, cost-effectiveness, and cost-benefit of delivering evidence- based medication-assisted outpatient treatment for opioid dependence. It will also advance the field by including innovative methods to consider a personalized treatment selection strategy and by exploring the cost- effectiveness of genetic screening prior to substance abuse treatment to identify patients most likely to benefit from medication-assisted treatments.